A relationship between pulmonary emphysema, proteolysis of alveolar tissue, and alpha-l-proteinase inhibitor (alpha-l-antitrypsin) deficiency has been clearly established. The objectives of this proposal are to investigate the mechanism by which the inhibitor normally functions, to determine the entire structure of the inhibitor and compare this with variants which are poorly secreted into the blood, and to establish the exact physiological roles of leukocyte and macrophage proteinases in digestion of the structural proteins of the lung. The methods to be used include the currently available techniques for protein purification. Affinity chromatography will be used as a major tool in the isolation of both proteinases and proteinase inhibitors.